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L Teyton

Publications and source records attributed to L Teyton.

51 records · Page 3Linked to original sources
PubMed1992

Invariant chain--a regulator of antigen presentation.

MHC class II molecules present internalized antigens to the immune system. They have long been known to associate with a polypeptide called the invariant chain. Recent findings have revealed that this polypeptide performs two functions. First, it prevents class II molecules from binding antigenic peptides at the site of synthesis of class II molecules in the endoplasmic reticulum.Second, it targets class II molecules to their destination in the endocytic pathway, where they pick up antigenic peptides derived from endocytosed antigens. Short sequences in the cytoplasmic portion of the invariant chain serve as subcellular address labels. The functions of the invariant chain help to explain how the immune system divides its defence against foreign pathogens between cytotoxic T cells and antibodies.

Journal Article↗
PubMed1992

Assembly and transport of MHC class II molecules.

At the surface of antigen-presenting cells MHC class I and class II molecules present peptides to respectively CD8+ and CD4+ T cells. MHC class I molecules acquire peptides right after synthesis in the endoplasmic reticulum. MHC class II molecules do not acquire peptides in the endoplasmic reticulum but instead associate with a third chain, the invariant chain which impedes peptide binding. Subsequently the invariant chain takes MHC class II molecules to the endosomal/lysosomal compartment thanks to a targeting signal retained in its cytoplasmic tail. It then dissociates from the MHC class II dimer to allow it to bind peptides.

Biological Transport, Active↗
PubMed1991

Autocrine stimulation of interleukin 1 in human adherent synovial lining cells: down regulation by interferon gamma.

Interleukin 1 (IL-1) exerts biological properties on various immune and nonimmune cell types and tissues and thus may play an important role during chronic inflammatory processes. Here we have examined the IL-1 biosynthesis in adherent synovial lining cell (ASLC) cultures obtained from patients with rheumatoid arthritis (RA). We report that ASLCs in culture showed heterogeneous endogenous levels of IL-1 alpha and beta expression. Recombinant interleukin 1 (rIL-1) alpha or beta induced increases of IL-1 alpha and beta mRNA and proteins levels in ASLCs. Although IL-1 synthesis is enhanced by rIL-1 treatment, no soluble IL-1 alpha or beta could be detected by specific enzyme-linked immunosorbent assays. A pretreatment with recombinant IFN gamma (rIFN gamma) down-regulated the effect of rIL-1 on IL-1 synthesis in ASLCs. Actinomycin D suppressed the endogeneous and rIL-1-induced IL-1 mRNA expression Indomethacin, in the presence of rIL-1 alpha or beta, up-regulates the level of expression of IL-1 beta in ASLCs pretreated with rIFN gamma, but has the opposite effect in non-pretreated cells. The increase of IL-1 gene expression by rIL-1 in human ASLCs from RA patients may contribute as an amplification of the disease progress. These studies may also explain the beneficial effects of IFN gamma in experimental models of IL-1-induced bone and cartilage degradation and in patients with diseases involving IL-1.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Intracellular transport of class II MHC molecules directed by invariant chain.

Three structural motifs in the invariant chain (li) control the intracellular transport of class II major histocompatibility complex molecules. An endoplasmic reticulum retention signal in the full-length li suggests a role for li in the alpha-beta heterodimer assembly. Another signal motif directs a truncated li, alone or associated with individual class II chains, to a degradation compartment by a pathway circumventing the Golgi. When this truncated li binds alpha-beta dimers, a third signal dominates, directing the complex by way of the Golgi to vesicles in the cell periphery, which may represent a subcompartment of recycling endosomes.

Antibodies, Monoclonal↗
PubMed1990

Invariant chain distinguishes between the exogenous and endogenous antigen presentation pathways.

Class I MHC molecules acquire peptides from endogenously synthesized proteins, whereas class II antigens present peptides derived from extracellular compartment molecules. This dichotomy is due to the fact that the invariant chain associates with class II molecules in the endoplasmic reticulum, preventing binding of endogenous peptides. The mutually exclusive binding of peptide and invariant chain to class II molecules suggests that the invariant chain might play a part in autoimmune disease.

Amino Acid Sequence↗
PubMed1989

Modulation of HLA class II antigen expression by transfection of sense and antisense DR alpha cDNA.

In the human there are three isotypic forms of MHC class II gene products (HLA-DR, -DQ, and -DP). The isotype-matched alpha-beta dimers are predominant but isotype-mismatched dimers can also be expressed (DR alpha-DQ beta). Here it is shown that the expression of the DR alpha-DQ beta dimer can be correlated to a high ratio of DR alpha/DR beta mRNA. The DR alpha chain expression was modulated by transfection of a sense and antisense DR alpha cDNA. Overexpression of DR alpha promoted the appearance of the DR alpha-DQ beta dimer. On the other hand, pre-existing DR alpha-DQ beta dimer expression was suppressed after antisense DR alpha cDNA transfection. Therefore, imbalanced expression of the alpha and beta chain from a given isotype could lead to the modification of HLA class II phenotype.

B-Lymphocytes↗
PubMed1988

Interleukin-1 alpha modulates collagen gene expression in cultured synovial cells.

The effects of porcine interleukin-1 (IL-1) alpha on collagen production were studied in cultured human rheumatoid synovial cells. Addition of 0.05-5 ng of IL-1/ml into the cultures resulted in a dose-dependent decreased rate of collagen released into the medium over 24 h. To determine whether this inhibition was due to secondary action of prostaglandin E2 (PGE2) secreted in response to IL-1, cultures were incubated in presence of various inhibitors of arachidonate metabolism. Depending on the cell strains, these inhibitors were able to suppress or diminish the effect of IL-1, suggesting that PGE2 is involved in the mechanism. Depression of collagen production caused by IL-1 mainly affected type I collagen and therefore led to a change in the type I/type III collagen ratio in the extracellular medium. Steady-state levels of mRNA for types I and III procollagens were estimated by dot-blot hybridization and compared with the amounts of respective collagens produced in the same cultures. IL-1 generally increased procollagen type I mRNA, but to a variable extent, as did indomethacin (Indo). Depending on the cell strain, the combination of indo and IL-1 could elevate the mRNA level of type I procollagen compared with Indo alone. These results did not correlate with the production rate of collagen in the medium, which was diminished by exposure to IL-1. The level of mRNA for collagen type III was not greatly changed by incubation with IL-1, and a better correlation was generally observed with the amount of type III collagen found in the medium. These data suggest that an additional control mechanism at translational or post-translational level must exist, counterbalancing the stimulatory effect of IL-1 on collagen mRNA transcription. It is likely that IL-1 could modulate the production of collagen in synovial cells by an interplay of different mechanisms, some of them limiting the effect of primary elevation of the steady-state mRNA level.

Bucladesine↗
PubMed1987

HLA DR, DQ, and DP antigen expression in rheumatoid synovial cells: a biochemical and quantitative study.

Because an increased expression of HLA class II antigens appears to be a central feature in local lesions of rheumatoid arthritis (RA), we have developed specific tools to quantify Ia expression in RA at both the protein and mRNA levels. An original dot immunobinding assay and a quick blot hybridization with chain-specific HLA class II probes allowed quantification of HLA DR antigens and chain transcripts on small-size samples of adherent synovial lining cells (ASLC) from normal individuals or RA patients. These methods associated with Western blot techniques detecting class II and beta-chain expression showed that ASLC from RA patients freshly put in short-term culture expressed greater amounts of class II transcripts and proteins than ASLC from controls. Class II proteins and mRNA rapidly disappeared in culture. Recombinant interferon-gamma (rIFN-gamma) induced their re-expression. A study of the kinetics and levels of the HLA-D products showed similar patterns of activation in RA patients and controls. A qualitative analysis of HLA class II antigens synthesized in ASLC after rIFN-gamma induction was performed by two-dimensional gel electrophoresis. It revealed a normal pattern for alpha- and beta-chains in ASLC from normal and RA patients, thus eliminating the possibility that abnormal protein structure of Ia antigen expressed on ASLC is responsible for the activation of T cell immune responses in RA. Nevertheless, the invariant chain exhibited a particular pattern in ASLC with additional basic spots, and this might interfere with transport and glycosylation of HLA class II antigens in such cells.

Antibodies, Monoclonal↗
PubMed1987

Immunoregulatory mediators in the pathogenesis of rheumatoid arthritis.

There is strong evidence for the participation of T cells, B cells and monocytes-macrophages in the local constitution of RA lesions. Such cells may create synovial damage either directly or indirectly through the secretion of mediators able to amplify immune responses and damage neighboring cells. Interleukin 1 (IL 1) can be found in RA lesions together with inhibitors of its action. Tumor necrosis factor (TNF) is another monokine able alone and in conjunction with IL 1 to stimulate bone resorption and inhibit proteoglycan synthesis. Interferon (IFN) is able to enhance the synthesis of both IL 1 and TNF in monocytes-macrophages and, in the case of IFN gamma, to induce the expression of HLA class II antigens in synovial cells. Interleukin 2 produced by activated T lymphocytes is able to induce lymphocyte proliferation and IFN gamma production. Prostaglandins produced by activated monocytes can block IL 2 and IFN gamma secretion. The exact role of this complex network of immunoregulatory mediators in the pathogenesis of RA deserves to be better elucidated.

Antigen-Presenting Cells↗
PubMed1986

A quantitative dot immunobinding assay for human HLA class II antigens using nitrocellulose membrane filters.

A quantitative method for the evaluation of human HLA-DR antigen expression has been developed. Cell membrane proteins were solubilized in Nonidet P-40 or deoxycholic acid detergent and diluted in a Triton X-100 containing sample buffer. The samples were subsequently spotted on a nitrocellulose membrane filter and fixed by immersion in isopropyl alcohol-acetic acid solution. The membrane was saturated in a 5% BSA blocking buffer and sequentially incubated with specific monoclonal anti-HLA-DR antibody, and 125I-labelled protein A. Each spot was then assayed for radioactivity in a gamma scintillation counter. Immunoadsorbant purified HLA-DR antigen was used to standardize the method and a reference dosage curve was established with serial dilutions of the purified HLA-DR antigen. The method permitted the detection of HLA-DR antigens with reproducibility in the ng range, in cellular extracts, physiological and pathological fluids, and in fractions eluted from affinity columns.

Cell Line↗
PubMed1984

[Cleidocranial dysostosis. Contribution to its study apropos of 2 personal cases (an isolated and a familial form)].

Cleidocranial dysostosis is a rare embryopathy affecting the whole osseous system. Anomalies predominate on skull, chest and dentition but the whole skeleton can be affected especially pelvic girdle and spine. An autosomal transmission is often demonstrable; isolated forms are very uncommon. We present two cases fortuitously diagnosed in our ward: a familial cleidocraniopelvic major form and an incomplete isolated form. The treatment must be especially oriented towards dental malformations.

Adolescent↗
PubMedDate not supplied

A novel HLA class II molecule (DR alpha-DQ beta) created by mismatched isotype pairing.

Human major histocompatibility complex (MHC) class II molecules are heterodimeric glycoproteins composed of non-covalently associated alpha and beta chains. Only isotype-matched alpha-beta associations have been described in man; these can occur either by cis- or trans-complementation (HLA-DR, DQ, DP). Here evidence is provided for the existence of a new type of hybrid molecule (DR alpha-DQ beta) arising by mixed-isotype pairing in human B-cell lines. Class II isotype-mismatched heterodimers have been recently reported in the mouse after transfection of class II genes, and our data demonstrate that such interisotypic pairing can occur in untransfected cells. This crosspairing greatly enhances the repertoire of the class II antigens that regulate immune responses and leads us to reconsider the HLA-disease association.

Antibodies, Monoclonal↗